Influenza A virus Matrix protein 1-specific T-cell receptor (Flu-M1 TCR)

The T-cell receptor (TCR) recognizing influenza-derived peptides presented on HLA class I is a critical immune sensor for detecting and eliminating influenza-infected cells. The most prominent and well-characterized example is the TCR specific for the GILGFVFTL epitope, an immunodominant and highly conserved peptide from the viral Matrix protein 1 (M1), presented by the HLA-A*02:01 allele (UniProt: P0DSE2; Frontiers in Immunology, 2019). This TCR often exhibits a "public" repertoire, characterized by conserved gene usage (typically TRAV27 and TRBV19) across different individuals, which underpins broad-spectrum, heterosubtypic immunity against various influenza strains (PNAS, 2016; Journal of Biological Chemistry, 2017). In the pharmaceutical industry, these TCRs are targeted for the development of universal influenza vaccines (such as Flu-v and M-001) and are utilized in TCR-engineered T-cell (TCR-T) therapies to provide durable protection against seasonal and pandemic influenza (NIH, 2015; Annals of Internal Medicine, 2020; MDPI, 2019). Upon binding the peptide-HLA complex, the TCR initiates a signaling cascade that activates CD8+ cytotoxic T lymphocytes, leading to the targeted destruction of infected cells and the secretion of pro-inflammatory cytokines like interferon-gamma (TandfOnline, 2024; Frontiers in Immunology, 2014). This target is essential for developing heterosubtypic immunity that can protect against seasonal drift and pandemic shift in influenza viruses (MDPI, 2018; Annals of Internal Medicine, 2020). The structural basis of this recognition involves a "peg-notch" mechanism where the TCR CDR3 loops interact with the peptide and the MHC alpha-helices (UniProt, 2019). Therapeutic challenges include the potential for viral escape through mutations in the peptide anchor residues, although the M1 epitope remains highly conserved across most human and avian strains (ASM, 2009; PNAS, 2016).

Other names

GILGFVFTL-specific T-cell receptorHLA-A*02:01-restricted influenza T-cell receptorA2-M1 T-cell receptorTRAV27/TRBV19 T-cell receptorInfluenza M1-specific TCR

Recognition of conserved influenza A virus peptides, such as the M1-derived GILGFVFTL epitope, presented by HLA class I molecules (e.g., HLA-A*02:01), which activates CD8+ T cells to lyse infected cells and secrete antiviral cytokines (UniProt, 2019; Frontiers in Immunology, 2014).